The objectives of the proposed research are to further develop new "thermospray" detectors for HPLC and to demonstrate the potential utility of these new detectors for the solution of significant biomedical problems. Techniques for high performance liquid chromatography (HPLC) have evolved rapidly during the past few years, and many important biomedical applications are now well established. It is generally recognized that the major factor limiting further rapid development of HPLC is the lack of suitable detectors for many potential applications. The "thermospray" technique was recently developed at the University of Houston as a means of coupling HPLC to mass spectrometry. Recent work has shown that this technique not only provides a particularly effective method for accomplishing the successful union of mass spectrometry with liquid chromatography, but also may provide a whole new generation of sensitive, reliable, and inexpensive detectors which are universally applicable to HPLC analyses of complex mixtures containing non-volatile and/or thermally labile molecules. Improved detectors for HPLC analyses of biological samples are needed in many areas of biomedical research. Specifically, the proposed research is reponsive to the needs expressed in the omnibus solicitation for the SBIR program as follows: National Cancer Institute, Division of Cancer Biology and Diagnosis, molecular separation technology; National Institute of General Medical Sciences, Cellular and Molecular Basis of Disease Program and the Physiology and Biomedical Engineering Program; and the National Institute of Mental Health, Instrumentation for Basic and Clinical Research. In Phase I the work will focus on further refining and evaluating the thermospray transport detector and on evaluating various other alternatives for developing practical "universal" HPLC detectors based on the thermospray technique. The proposed work should result in the development of at least one commercially viable new LC detector during Phase I, and in a clear definition of the favored approaches to be developed in Phase II. The anticipated long-range result of the Phase II program is a new family of commercially available universal and selective detectors for HPLC which will allow this powerful technique to be applied to a wider variety of important biomedical problems.